Hyperthermia, 41-44 C, has been shown to potentiate the cellucidal effects of x-radiation. The combination of local hyperthermia and x-radiation is now being used in therapeutic programs for the treatment of a variety of malignancies. At the present time there is no data to indicate whether hyperthermia will alter the carcinogenic potential of ionizing radiation. Twenty-four groups of mice will be exposed to either single or multiple (6 fractions) exposures of x-radiation to the leg. One half of the animals will also have the irradiated leg made hyperthermic for 45 minutes immediately following the x-radiation. Temperatures of 37, 39, 41 or 43 will be used. The incidence, time of onset and the histological identity of the tumors developing at the treated site will be determined. Tumor growth rate and the presence of malignancies in other tissues will be observed. The acute and late skin reactions will also be measured to determine whether a moderate degree of hyperthermia may accelerate the repair of radiation damage rather than potentiate it. Preliminary observations by the PI indicate that the local x-radiation followed by moderate hyperthermia (39 or 40 C) significantly increase the risk of radiation induced tumors. All the treatment groups as per the experimental protocol have completed their hyperthermia and/or radiation treatments. For single treatments, hyperthermic temperatures of 37, 39 or 41 C tended to accelerate the repair of radiation damage as measured by the acute skin reactions. A hyperthermic temperature of 43 C potentiated the radiation reaction (thermal enhancement factor 1.1). When the hyperthermia 37 or 39 C and radiation were given in six fractions there was no change in the skin reaction compared to x-irradiation alone. Hyperthermic temperatures of 41 or 43 resulted in a significant thermal enhancement of 1.16 or 1.36.